The effect of low-and high-dose adjunctive mitomycin C in trabeculectomy

Selenium is a powerful antioxidant regulating the activity of the glutathione peroxidase enzymes, which catalyse the detoxification of hydrogen peroxide and organic hydroperoxides. Selenium deficiency has been implicated in the aetiopathogeny of Keshan disease, an endemic cardiomyopathy observed in China, and in other cases of congestive cardiomyopathy in subjects on artificial nutrition. However, the evidence from case-control and prospective studies for an association between low selenium status and cardiovascular diseases remains controversial. Mechanisms whereby selenium protects against such diseases include increased resistance of low-density lipoproteins against oxidative modification, modulation of prostaglandin synthesis and platelet aggregation, and protection against toxic heavy metals. The therapeutic benefit of selenium administration in the prevention and treatment of cardiovascular diseases still remains insufficiently documented.     

Phytoremediation: a novel strategy for the removal of toxic metals from the environment using plants

Toxic metal pollution of waters and soils is a major environmental problem, and most conventional remediation approaches do not provide acceptable solutions. The use of specially selected and engineered metal-accumulating plants for environmental clean-up is an emerging technology called phytoremediation. Three subsets of this technology are applicable to toxic metal remediation: (1) Phytoextraction--the use of metal-accumulating plants to remove toxic metals from soil; (2) Rhizofiltration--the use of plant roots to remove toxic metals from polluted waters; and (3) Phytostabilization--the use of plants to eliminate the bioavailability of toxic metals in soils. Biological mechanisms of toxic metal uptake, translocation and resistance as well as strategies for improving phytoremediation are also discussed.     

Barriers and pathways to testing among HIV-infected women

N-acetylcysteine (NAC), the acetylated variant of the amino acid L-cysteine, is an excellent source of sulfhydryl (SH) groups, and is converted in the body into metabolites capable of stimulating glutathione (GSH) synthesis, promoting detoxification, and acting directly as free radical scavengers. Administration of NAC has historically been as a mucolytic agent in a variety of respiratory illnesses; however, it appears to also have beneficial effects in conditions characterized by decreased GSH or oxidative stress, such as HIV infection, cancer, heart disease, and cigarette smoking. An 18-dose oral course of NAC is currently the mainstay of treatment for acetaminophen-induced hepatotoxicity. N-acetylcysteine also appears to have some clinical usefulness as a chelating agent in the treatment of acute heavy metal poisoning, both as an agent capable of protecting the liver and kidney from damage and as an intervention to enhance elimination of the metals.     

Interpersonal and self-reported hostility among combat veterans with and without posttraumatic stress disorder

Despite the low concentrations of heavy metals in the surrounding medium, aquatic organisms take them up and accumulate them in their soft tissues to concentrations several fold higher than those of ambient levels (Bryan 1979; Rainbow et al. 1990). Knowledge of accumulation patterns of a particular trace metal is a prerequisite for understanding the significance of an observed metal concentration in a particular animal, especially from the aspect of biomonitoring. Many marine invertebrates accumulate heavy metals without any regulation and the accumulation necessarily being associated with mechanisms to store the metals in a detoxified form. Two detoxification mechanisms have been described, both of which may occur in one specimen. Heavy metals can either be bound up in insoluble metalliferous 'granules' (Mason and Nott 1981), or are bound to soluble metal-binding ligands, such as metallothioneins (Roesijadi 1992). Some marine decapod crustaceans have an innate ability to regulate the internal concentrations of essential but potentially toxic metals within a constant level, presumably to meet their metabolic demands (Rainbow 1985, 1992). However, at present, there is no such information relating to freshwater decapod crustaceans, especially shrimps which occupy a totally different environment. Macrobrachium malcolmsonii (Milne Edwards), a potential aquaculture species for freshwater is found in abundance in one of the major Indian rivers, the Cauvery. In the present study, an attempt was made to determine whether the freshwater prawn, M. malcolmsonii, is able to regulate the three essential elements, copper, chromium and zinc, over a wide range of dissolved concentrations. These three metals were chosen because the Cauvery River receives pollutants containing these metals (Vijayram et al. 1990).     

Microbial leaching in environmental clean-up programmes

Microbial leaching is a simple and effective technology for extracting valuable metals from low-grade ores and mineral concentrates. Besides the industrial application for raw materials supply, microbial leaching has some potential for remediation of mining sites, treatment of mineral industrial waste products, detoxification of sewage sludge and for remediation of soils and sediments contaminated with heavy metals. There is no routine treatment for toxic metals dispersed in solid materials, and autotrophic and heterotrophic leaching processes may be considered for environmental clean-up programmes. The problems of bioremediation for heavy metal-contaminated sites are very different from those of bioremediation for organic pollution, but intensive interdisciplinary collaboration in basic and applied research in this economically important field is expected to be very beneficial in the near future. It would be ideal if the bioremediation system maximised the extent and rate of degradation of waste materials, simultaneously minimising the level of toxic substances during the operation.     

Gastrointestinal absorption of metals

Estimating gastrointestinal absorption remains a significant challenge in the risk assessment of metals. This presentation reviews our current understanding of the gastrointestinal absorption of lead (Pb) to illustrate physiological mechanisms involved in metal absorption, new approaches that are being applied to the problem of estimating metal absorption in humans, and issues related to integrating this information into risk assessment. Absorption of metals can be highly variable in human populations because it is influenced by a variety of factors that include the chemical form of the metal, environmental matrix in which the ingested metal is contained, gastrointestinal tract contents, diet, nutritional status, age, and, in some cases, genotype. Thus, in risk assessment models, gastrointestinal absorption is best described as a variable whose distribution is determined in part by the above multiple influences. Although we cannot expect to evaluate empirically each of the above factors in human populations, we can expect to achieve a sufficiently detailed understanding of absorption mechanisms to develop conceptual and, eventually, quantitative models of absorption that account for some aspects of individual variability. A conceptual model is presented of the physiological processes involved in the transfer of ingested metals from the lumen of the gastrointestinal tract to the blood circulation. Components of the model include delivery to the site(s) of absorption; distribution among intracellular and extracellular ligands and transcellular and paracellular pathways of transfer across the gastrointestinal tract epithelium. The gastrointestinal absorption of Pb is discussed in the context of this model.     

Localization of neutral endopeptidase in the ovine uterus and conceptus during the oestrous cycle and early pregnancy

Allylamine (AA) is an electrophilic amine with a long history of experimental usage because of its extremely potent and relatively specific cardiovascular toxicity; it has been utilized in a variety of experimental models attempting to mimic human atherosclerotic lesions, myocardial infarction, and vascular injury. Even though the exact mechanisms by which AA causes vascular lesions remain unresolved, recent studies on the acute effects of AA exposure in rats strongly suggest that deamination to the aldehyde acrolein, oxidative stress, and the resultant increase in lipid peroxidation, generation of .OH radicals, and acute depletion of glutathione (GSH) may be some of the causative factors in AA-induced vascular lesions. Since glutathione S-transferase 8-8 (GST8-8) of rat belongs to a distinct subgroup of GST isozymes involved in the detoxification of products of lipid peroxidation, we designed studies to examine the effects of AA exposure on this GST isoform in rat aorta using Western blotting and immunohistochemical techniques. The results of these studies demonstrate that GST8-8 is expressed in rat aorta and is dramatically induced upon AA exposure. By immunohistochemistry, GST8-8 was localized in the smooth muscle cells of the vascular media which is believed to be the site of metabolism of AA. A significant increase in gamma-glutamylcysteine synthetase activity and GST activity toward 4-hydroxynonenal and acrolein, which are preferred substrates of GST8-8, was seen as early as 3 days following AA treatment. Alterations in GSH and other GSH-related enzymes at 3 and 10 days support the concept that--upon AA exposure--aortic defense mechanisms respond early and induction of GSH biosynthesis and rat GST8-8 occur to alleviate the toxic effects of acrolein, a major, genotoxic product of AA metabolism. The presence of GST8-8 in the vasculature, which is constantly exposed to products of lipid peroxidation, and its induction by AA, suggest that GST8-8 plays a key role in protecting blood vessels against oxidative stress and hence, may be involved in the atherogenic process.     

Glutathione defense in non-parenchymal cells

Toxicity to nonparenchymal cells can result in disruption of the hepatic microcirculation, altered production of cytokines, and hepatic fibrosis. Many of the relevant insults produce oxidative stress or toxic metabolites that require glutathione detoxification. This article reviews the role of sinusoidal endothelial cell glutathione (GSH) in reperfusion injury, cytomegalovirus infection, and hepatic venoocclusive disease. The effects of oxidative stress and antioxidants on Kupffer cell production of cytokines and, in particular the potential benefit of antioxidants in the setting of reperfusion injury, are discussed. Oxidative stress upregulates collagen gene expression by stellate cells, and this is modulated by antioxidants. Current thinking on intrahepatic GSH and cysteine homeostasis is discussed. Finally, I review the published data on nonparenchymal GSH levels, glutathione S-transferase activity and isoenzyme pattern, and glutathione peroxidase activity.     

Individual susceptibility to inhaled pollutants--identification, mechanisms and public health policy implications

In every community, there are individuals whose chances of illness or accident are greater than those of others. In susceptible persons, adverse health effects occur at a lower exposure than in the majority of population. The reason for this, though often weak, can usually be ascertained. The paper focuses primarily on host factors that may increase an individual's susceptibility to air pollutants present in the general environment. These factors include genetic background, age, gender, nutritional status, physiological status, presence of coexisting lung disease, and lifestyle. They relate to various mechanisms of individual susceptibility to air pollutants from the environment into the body, to alterations in detoxification and immunological reactions, and to variations in the responsiveness of lung tissues. Several epidemiological techniques to detect biological events relevant to host susceptibility and disease progression are mentioned. They are mainly based on genetic traits, host characteristics, pulmonary function tests, biochemical and immune changes. Measuring the variations in risk among susceptible individuals is necessary to assess correctly respiratory health risk due to inhaled pollutants at the population level, and subsequently to develop rational public health policy to reduce the incidence of those diseases in a given population. Before being able to formulate this policy, however, one must know how to detect those individuals who are susceptible to air pollutants.     

Metal ion homeostasis and intracellular parasitism

Bacteria possess multiple mechanisms for the transport of metal ions. While many of these systems may have evolved in the first instance to resist the detrimental effects of toxic environmental heavy metals, they have since become adapted to a variety of important homeostatic functions. The 'P'-type ATPases play a key role in metal ion transport in bacteria. A Cu+-ATPase from the intracellular bacterium Listeria monocytogenes is implicated in pathogenesis, and similar pumps in Mycobacterium tuberculosis and M. leprae may play a comparable role. Intracellular bacteria require transition metal cations for the synthesis of superoxide dismutases and catalases, which constitute an important line of defence against macrophage-killing mechanisms. The macrophage protein Nramp1, which confers resistance to a variety of intracellular pathogens, has also been shown recently to be a divalent amphoteric cation transporter. Mycobacterial homologues have recently been identified by genomic analysis. These findings suggest a model in which competition for divalent cations plays a pivotal role in the interaction between host and parasite.     

Acute toxicity, toxicokinetics, and tissue target of lead and uranium in the clam Corbicula fluminea and the worm Eisenia fetida: comparison with the fish Brachydanio rerio

The general objective of our work was to propose new reference material for chemical toxicity testing and new sentinel organisms for environmental quality survey programs (freshwater or soils). We also wanted to provide basic toxicological data on the environmental effects of uranium. Thus, we conducted a comparative study to establish the acute toxicity and toxicokinetics of lead (Pb) and uranium (U) to the bivalve mollusc Corbicula fluminea and the terrestrial annelid Eisenia fetida andrei and to compare these findings with those of the well-known teleost fish Brachydanio rerio. We then measured the concentration of these metals in various tissues of the clam and the worm after two periods of exposure (4 and 11 days) to identify the affinities of these tissues for Pb and U. Our results have shown that Pb and U are very toxic to Eisenia and relatively nontoxic to Corbicula. By comparison, Pb was relatively nontoxic and U appeared to be very toxic to the fish. The toxicokinetic studies indicated that the three species are able to accumulate Pb and U, the rate and level of accumulation depending both on the species and the metal. We also found that fish and clams depurate the two metals. Data collected for the worm were conflicting: Pb was not depurated whereas tissue concentrations of U declined after the eighth day of exposure. Our study has also shown that the tissue distribution of Pb in the mollusc and in the earthworm differs significantly from that of U, both after 4 and 11 days exposure. In conclusion, these three species showed potential as bioindicators of environmental contamination by metals. Indeed, they could be used in conjunction to test different compartments of an ecosystem: worms for soils, fish for the water column, and clams for the water/sediment interface.     

Bacterial catalytic processes for transformation of metals

Microorganisms actively participate in the transformation of metals and metalloids by various processes including adsorption, absorption, alkylation, oxidation and reduction reactions. Bacteria of the genera Thiobacillus and Sulfolobus have a chemolithotrophic mode of metabolism and catalyze various metal transformations. These bacteria are primarily involved in oxidation-reduction reactions of metals. Metal sulfides can be either directly oxidized by the microbes or oxidized by ferric iron, an end-product of microbial metabolism. These processes result in solubilization of iron, copper, molybdenum, uranium, and many other metals as well. Bacteria capable of these reactions are found, and they function in a variety of environments. Conditions which favor their growth are acidic pH (1.5 to 3.5) and temperatures which can be as high as 75 degrees C for Sulfolobus. The microbes have potential for mobilization of pollutants, or toxic elements, during resource extraction processes. In the absence of oxygen, iron, molybdenum and chromium may be reduced by microbes.     

植物修复重金属污染土壤的技术进展

土壤重金属污染的危害日趋普遍和严重,使用传统的物理、化学修复方法成本高,对环境扰动大,利用以阳光为能源的植物去修复被重金属污染的土壤是一种有应用前景的技术.为了了解植物修复的应用现状与进展,对近年来国内外在这方面的研究工作进行了综述,介绍了常用于修复重金属污染土壤的几类植物,并对这些植物及它们的不同部位对不同重金属的累积效果和影响修复效果的因素作了概括,并介绍了如何提高植物的修复效率.对累积了重金属的植物目前的处理方法也做了介绍,当前对植物的处理方法做的研究较少,还有待更多的探索研究.植物修复具有成本低、利于土壤生态系统的保持等优点,但也有其不足之处.为了更好地修复被重金属污染的土壤,还需要对植物修复做进一步的研究与改进.     

Women and menopause: beliefs, attitudes, and behaviors. The North American Menopause Society 1997 Menopause Survey

It has been demonstrated that exposure to mercury or cadmium compounds causes alterations in the glutathione system in a model glial cell line, C6. Here we report that two organic tin compounds, triethyltin (TET) and trimethyltin (TMT), are also toxic to these cells with EC50 values for cell death of c. 0.02 microM and 0.8 microM respectively. Exposure for 24 h to either of these compounds at sub-toxic concentrations caused increases in the amount of reduced glutathione (GSH) per cell. Increases in glutathione-S-transferase enzyme activity were also demonstrated after TET or TMT exposure. This suggests that glutathione increases occur in glial cells after toxic insults below that required to cause cell death, possibly acting as a protective mechanism. To test whether GSH plays a role in organotin-induced cell death we manipulated GSH in the culture media or via intracellular GSH and looked at the effects on sensitivity to TET or TMT toxicity. Adding GSH to the culture media did not protect the cells. Depletion of intracellular GSH with buthionine-[S,R] sulphoximine did not alter cytotoxicity of TET or TMT. However, pre-treatment with (-)-2-oxo-4-thiazolidine carboxylic acid (OTC), which increases intracellular GSH levels, protected the cells against both compounds. The EC50 for TMT was increased from 0.77 to 1.8 microM, a 2.3-fold shift, whereas the EC50 for TET was increased > 20-fold, from 0.022 to 0.47 microM. One interpretation of these results is that GSH protects cells against the toxicity of organic tin compounds without reacting directly with them to any significant extent. Under conditions where GSH is depleted, additional protective mechanisms may be active.     

Toxicokinetics and biochemistry of cadmium with special emphasis on the role of metallothionein

Cadmium is a toxic metal with extremely long biological half-time of 15-20 years in humans. It has for decades been known that cadmium exposure can cause a variety of adverse health effects, among which kidney dysfunction, lung diseases, disturbed calcium metabolism and bone effects are most prominent. Following long term exposure the kidney is the critical organ. Cadmium and its compounds give rise to lung cancer after inhalation and have been classified as human carcinogens. Metallothionein (MT) is a low-molecular -weight protein, 6500Da with high cysteine content and high metal affinity, which plays a major role in the kinetics and metabolism of cadmium. The balance between CdMT and non-bound Cd in renal tissue has been shown to be of crucial importance for expression of toxicity. The most well studied metallothioneins are metallothioneins I and II with their isoforms which are expressed in almost all mammalian tissues. Metallothionein III is expressed in brain and is rich in zinc. Since the blood-brain barrier keeps Cd outside the CNS, reported neurotoxic effects of Cd during development are likely to be secondary to an interference of Cd with Zn-metabolism and not a direct effect of Cd on brain cells. It is therefore of importance to investigate whether neurotoxicity induced by cadmium is related to mechanisms involving MT III in brain.